Background:

Immunotherapy drugs help the body to fight cancer. Scientists think that combining some of these drugs will make them work better than when used alone. This may be true for many types of cancer, including castration-resistant prostate cancer (CRPC).

Objective:

To test if any of the combinations of drugs below have anti-prostate cancer activity and to test if they are safe.

1. Bavarian-Nordic (BN)-brachyury, bintrafusp alfa (M7824).
2. Bavarian-Nordic (BN)-brachyury, bintrafusp alfa (M7824) + Anktiva (N-803).
3. Bavarian-Nordic (BN)-brachyury, bintrafusp alfa (M7824) + Anktiva (N-803) + Epacadostat.

Eligibility:

People ages 18 and older with CRPC or another metastatic cancer

Design:

Participants will be screened with:

• Medical history
• Physical exam
• Computed tomography (CT) or magnetic resonance imaging (MRI) scans
• Possible bone imaging
• Blood, urine, and heart tests
• Possible tumor biopsy

Participants will be treated with a 2-, 3- or 4-drug combinations of the following study drugs in 2-week cycles:

• Participants will receive M7824 by intravenous (IV) once every 2 weeks.
• Participants will receive N-803 by injection once every 2 weeks. They will record any skin changes at the injection site in a diary.
• Participants will receive BN-brachyury as 4 injections to different limbs. They will get the first 3 doses 2 weeks apart. Then they will get doses every 4 weeks for 6 months, then every 3 months for 2 years, then every 6 months.
• Participants will take Epacadostat orally every 12 hours. They will keep a pill diary.

Participants will have physical exams and blood and urine tests at the start of each cycle. They may have scans every 12 weeks.

Participants will continue treatment until their disease gets worse or they cannot tolerate the side effects.

Participants will have a follow-up visit 4-5 weeks after they stop treatment. They will have a physical exam and blood tests. They may be asked to return for scans every 3 months.